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Shao D.,Rutgers University | Oka S.-I.,Rutgers University | Brady C.D.,Rutgers University | Haendeler J.,IUF Leibniz Research Institute for Environmental Medicine | And 2 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2012

Oxidative stress is presumed to be involved in the pathogenesis of many diseases, including cardiovascular disease. However, oxidants are also generated in healthy cells, and increasing evidence suggests that they can act as signaling molecules. The intracellular reduction-oxidation (redox) status is tightly regulated by oxidant and antioxidant systems. Imbalance between them causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, leading to dysregulation. In this review, we will briefly summarize the aspects of ROS generation and neutralization mechanisms in the cardiovascular system. ROS can regulate cell signaling through oxidation and reduction of specific amino acids within proteins. Structural changes during post-translational modification allow modification of protein activity which can result in altered cellular function. We will focus on the molecular basis of redox protein modification and how this regulatory mechanism affects signal transduction in the cardiovascular system. Finally, we will discuss some techniques applied to monitoring redox status and identifying redox-sensitive proteins in the heart. This article is part of a Special Section entitled "Post-translational Modification.". © 2011 Elsevier Ltd.


Reinke H.,Heinrich Heine University Düsseldorf | Reinke H.,IUF Leibniz Research Institute for Environmental Medicine | Asher G.,Weizmann Institute of Science
Gastroenterology | Year: 2016

The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis. © 2016 AGA Institute.


Krutmann J.,IUF Leibniz Research Institute for Environmental Medicine | Morita A.,Nagoya City University | Chung J.H.,Seoul National University
Journal of Investigative Dermatology | Year: 2012

The health consequences of sun exposure have concerned mankind for more than 100 years. Recent molecular studies in photodermatology have greatly advanced our understanding of this important topic. We will illustrate this progress by focusing on the following selected topics: (i) the nature of the DNA damage-independent part of the UVB response of human skin and the role of the arylhydrocarbon receptor in cutaneous biology, (ii) the contribution of wavelengths beyond the UV spectrum to solar radiation-induced skin damage, (iii) the emerging evidence that subcutaneous fat is a target tissue for sunlight, and (iv) the most recent insight into the mode of action of phototherapy. © 2012 The Society for Investigative Dermatology.


Vierkotter A.,IUF Leibniz Research Institute for Environmental Medicine | Krutmann J.,IUF Leibniz Research Institute for Environmental Medicine
Dermato-Endocrinology | Year: 2012

Skin aging does not only occur by passing time alone but also by the exposure to different environmental factors. The skin aging process, which is induced by environmental factors, is named premature or extrinsic skin aging process and can be distinguished from the chronologically (intrinsic) skin aging process by characteristic skin aging signs. Well known environmental factors leading to extrinsic skin aging are sun exposure and smoking. Recently, an epidemiological study could further discover an association between air pollution and skin aging. First of all the skin aging inducing effect of sun exposure was discovered and an own term (photoaging) was given to this special field of extrinsic skin aging. Mechanistic studies have further increased our knowledge about the molecular pathways by which environmental factors contribute to extrinsic skin aging. In this regard, profound knowledge how sun exposure leads to extrinsic skin aging were gained in the last years, and additionally there are also indications how smoking and air pollution might contribute to this process. Moreover it was realized that extrinsic skin aging manifests differently between different populations. Thus, in this review we summarize the influence of the different environmental factors: sun exposure, smoking and air pollution on skin aging and further present ethnic-specific manifestations of extrinsic skin aging. © 2012 Landes Bioscience.


Van Berlo D.,IUF Leibniz Research Institute for Environmental Medicine | Clift M.,University of Fribourg | Albrecht C.,IUF Leibniz Research Institute for Environmental Medicine | Schins R.,IUF Leibniz Research Institute for Environmental Medicine
Swiss Medical Weekly | Year: 2012

After the health catastrophe resulting from the widespread use of asbestos which was once hailed as a new miracle material, the increasing use of carbon nanotubes (CNTs) has spawned major concern due to their similarities in terms of size, shape and poor solubility. Assessment of genotoxicity has shown that CNTs can damage DNA in vitro and in vivo. The genotoxic potential of different CNT samples varies considerably, however, with negative findings reported in a number of studies, probably due to the enormous heterogeneity of CNTs. The observed spectrum of genotoxic effects shows similarities with those reported for asbestos fibres. Mutagenicity has been found in vivo but in bacterial assays both asbestos and CNTs have mostly tested negative. An overview of key experimental observations on CNT-induced genotoxicity is presented in the first half of this review. In the second part, the potential mechanisms of CNT-elicited genotoxicity are discussed. Whereas CNTs possess intrinsic ROS-scavenging properties they are capable of generating intracellular ROS upon interaction with cellular components, and can cause antioxidant depletion. These effects have been attributed to their Fenton-reactive metals content. In addition, CNTs can impair the functionality of the mitotic apparatus. A noteworthy feature is that frustrated phagocytosis, which is involved in asbestos-induced pathology, has been observed for specific CNTs as well. The involvement of other mechanisms generally implicated in particle toxicity, such as phagocyte activation and impairment of DNA repair, is largely unknown at present and needs further investigation.


Schiavi A.,IUF Leibniz Research Institute for Environmental Medicine | Schiavi A.,University of Rome Tor Vergata | Ventura N.,Heinrich Heine University Düsseldorf | Ventura N.,IUF Leibniz Research Institute for Environmental Medicine | Ventura N.,University of Rome Tor Vergata
Experimental Gerontology | Year: 2014

Mitochondria are highly dynamic organelles which play a central role in cellular homeostasis. Mitochondrial dysfunction leads to life-threatening disorders and accelerates the aging process. Surprisingly, on the other hand, a mild reduction of mitochondria functionality can have pro-longevity effects in organisms spanning from yeast to mammals. Autophagy is a fundamental cellular housekeeping process that needs to be finely regulated for proper cell and organism survival, as underlined by the fact that both its over- and its defective activation have been associated with diseases and accelerated aging. A reciprocal interplay exists between mitochondria and autophagy, which is needed to constantly adjust cellular energy metabolism in different pathophysiological conditions. Here we review general features of mitochondrial function and autophagy with particular focus on their crosstalk and its possible implication in the aging process. © 2014 Elsevier Inc.


Eckers A.,IUF Leibniz Research Institute for Environmental Medicine | Haendeler J.,IUF Leibniz Research Institute for Environmental Medicine | Haendeler J.,Central University of Costa Rica
Antioxidants and Redox Signaling | Year: 2015

According to the World Health Organization, from 2014, cardiovascular diseases (CVD) are the number one cause of death worldwide. One of the key players in maintaining proper cardiovascular function is the endothelium, the inner layer of all blood vessels. This monolayer of cells on one hand serves as a barrier between blood and the surrounding tissue and on the other hand regulates many aspects of vessel function. Therefore, it is not surprising that interventions reducing the risk for CVD improve endothelial function. There is a clear correlation between endothelial dysfunction, in which the endothelial homeostasis is disturbed, and the development and progression of many CVD. Thus, the development of diagnostic tools for early detection of disturbances in endothelial homeostasis or interventions aimed at improving endothelial function after insults require a comprehensive knowledge not only of the cellular reactions to the positive or negative stimuli but also of the molecular mechanisms relaying these responses. Thus, this Forum on "endothelial cells in health and disease" focuses on key molecules and processes intimately involved in endothelial cell function and covers areas from endothelial nitric oxide synthase-dependent processes, over the group of Phox-Bem1 domain proteins, cytochrome P450 epoxygenase-derived metabolites, and pre-mRNA splicing to microRNAs. Finally, one has to conclude that keeping endothelial homeostasis is the central key for a healthy long life of the human individual. © Copyright 2015, Mary Ann Liebert, Inc.


Haarmann-Stemmann T.,IUF Leibniz Research Institute for Environmental Medicine | Boege F.,Heinrich Heine University Düsseldorf | Krutmann J.,IUF Leibniz Research Institute for Environmental Medicine
Journal of Investigative Dermatology | Year: 2013

In this issue, Matsuda et al. demonstrate the protective effect of mild heat preconditioning on UVB-induced photoaging in SKH-1 hairless mice. Mild heat exposure stimulates the upregulation of HSP70 chaperones, which inhibit the activities of matrix-degenerating enzymes, thereby avoiding wrinkle formation. This newly identified heat-mediated process of adaptation to UVB radiation exposure opens new opportunities to slow extrinsic skin aging. © 2013 The Society for Investigative Dermatology.


Grether-Beck S.,IUF Leibniz Research Institute for Environmental Medicine | Marini A.,IUF Leibniz Research Institute for Environmental Medicine | Jaenicke T.,IUF Leibniz Research Institute for Environmental Medicine | Krutmann J.,IUF Leibniz Research Institute for Environmental Medicine
Photodermatology Photoimmunology and Photomedicine | Year: 2014

Summary: Photoprotection of human skin by means of sunscreens or daily skin-care products is traditionally centered around the prevention of acute (e.g. sunburn) and chronic (e.g. skin cancer and photoaging) skin damage that may result from exposure to ultraviolet rays (UVB and UVA). Within the last decade, however, it has been appreciated that wavelengths beyond the ultraviolet spectrum, in particular visible light and infrared radiation, contribute to skin damage in general and photoaging of human skin in particular. As a consequence, attempts have been made to develop skin care/sunscreen products that not only protect against UVB or UVA radiation but provide photoprotection against visible light and infrared radiation as well. In this article, we will briefly review the current knowledge about the mechanisms responsible for visible light/infrared radiation-induced skin damage and then, based on this information, discuss strategies that have been successfully used or may be employed in the future to achieve photoprotection of human skin beyond ultraviolet radiation. In this regard we will particularly focus on the use of topical antioxidants and the challenges that result from the task of showing their efficacy. © 2014 John Wiley & Sons A/S.


Haarmann-Stemmann T.,IUF Leibniz Research Institute for Environmental Medicine | Esser C.,IUF Leibniz Research Institute for Environmental Medicine | Krutmann J.,IUF Leibniz Research Institute for Environmental Medicine | Krutmann J.,Heinrich Heine University Düsseldorf
Journal of Investigative Dermatology | Year: 2015

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor expressed in all skin cell types, which is critically involved in the pathogenesis of a variety of skin diseases and thus represents a potential therapeutic target. Recent studies indicate that blocking AHR activation is desirable in some skin conditions, whereas the opposite, i.e., stimulation of AHR activation, is beneficial in another group of skin disorders. We here propose a model based on qualitative differences in canonical versus non-canonical AHR signaling to reconcile these seemingly contradictory observations. © 2015 The Society for Investigative Dermatology.

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